Universal 25 µg/L Threshold for Iron Deficiency is Cost-Effective, Could Improve Management in US Women

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New research from Yale School of Medicine provides insight into potential avenues to improve the diagnosis and management of iron deficiency among adult women in the United States.

A cost-effectiveness analysis examining varying ferritin thresholds for diagnosing iron deficiency, results indicate use of a 25 µg/L threshold for diagnosing iron deficiency in adult women was a cost-effective intervention, regardless of whether these patients received subsequent treatment with oral or intravenous iron supplementation.¹

“Our models show that setting this threshold at 25 μg/L would improve the quality of life for numerous individuals and do it for cents on the dollar,” said lead investigator, Daniel Wang, a medical student at the Yale School of Medicine, in a press release.² “The incremental cost-effectiveness ratio of this strategy compared to no screening is well below all accepted willingness-to-pay thresholds in the US.”

A significant burden on population-level health and public health systems, iron deficiency is linked to adverse effects on social, emotional, and health-related well-being of affected individuals, as Wang and team note in the current study. Citing the absence of universal screening for adult women in the US, Wang and George Goshua, MD, MSc, of Hematology-Oncology and Yale CORE at the Yale School of Medicine and Yale Cancer Center, launched the current study to estimate the potential benefit of varying thresholds for diagnosis.¹

The study, which investigators purport is the first cost-effectiveness analysis of varying ferritin thresholds for iron deficiency diagnosis and treatment, was presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition.¹

For the purpose of analysis, investigators designed Markov simulation model of adult women within the US to assess the cost-effectiveness of 3 iron deficiency screening strategies, which were defined by a ferritin threshold of less than 25 µg/L, a ferritin threshold of less than 15 µg/L, and no screening. The investigators’ model used a lifetime time horizon with a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY) and costs were assessed in 2024 US dollars, which was determined using the US Medical Expenditures Panel Survey.¹

Investigators leveraged National Health and Nutrition Examination Survey data for cycles spanning 2003 through 2010 and 2015 through 2020 to identify the epidemiological prevalence of iron deficiency whereas randomized clinical trials and the World Health Organization’s Vigibase to determine the probability of adverse events. Investigators pointed out once daily oral ferrous sulfate was used as the base-case iron supplement for treatment of iron deficiency and a scenario analysis examined treatment with intravenous iron dextran, with effectiveness measured in QALY.¹

The study's primary outcome was the incremental cost-effectiveness ratio (ICER) of the different screening approaches relative to no screening.¹

Upon analysis of the base case scenario, results suggested screening for iron deficiency with a ferritin threshold of less than 25µg/L was the cost-effective strategy in 100% of 10,000 Monte Carlo iterations, with $212,000 in costs and generating 24.3 QALYs compared $211,000 and 23.3 QALYs at the less than 15µg/L threshold and $210,000 and 22.3 QALYs relative to no screening. Investigators highlighted the ICER of 25µg/L compared to no screening is $940 per QALY and “well under” all accepted willingness-to-pay thresholds in the US.¹

Investigators called attention to results pointing to similar cost-effectiveness when patients with iron deficiency were treated with iron dextran. Additionally, data from a deterministic sensitivity analysis suggested no parameter variations changed the study conclusion.¹

“The current reference ranges we have for ferritin are outdated and come from a biased sample; a majority of hematologists agree that the current threshold is far too low,” Wang explained.² “We need to recognize that this is an issue for all persons with the capacity to menstruate, and we need to raise the bar on determining the proper cutoff and effectively disseminate that information to care providers and labs.”

References:

1. Wang D, Glaeser-Khan S, Wang DY, et al. Sex, Lies, and Iron Deficiency in 2024: Cost-Effectiveness of Screening Ferritin Thresholds for the Treatment of Iron Deficiency in Women of Reproductive Age. Presented at: 66th American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10; San Diego, California.
2. American Society of Hematology. Putting women and children first to optimize their Hematology Health. Hematology.org. December 7, 2024. Accessed December 8, 2024. https://www.hematology.org/newsroom/press-releases/2024/putting-women-and-children-first-to-optimize-their-hematology-health.